Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. Gout results from the body's reaction to urate crystals deposited in tissues, and this pathophysiology is well understood. If used appropriately, available therapies can be entirely effective in not only treating the symptoms of gout, but also in eliminating the excess urate from the body, thereby eradicating the disease. Because of these facts, management of patients with gout should be successful. However, management of gout is particularly challenging in the elderly, even though the principles of management are the same for all age groups. The purpose of this article is to review these principles and discuss them as they pertain to the elderly. The classic gout attack is acute in onset, extremely painful and associated with marked swelling, warmth, erythema and tenderness of a single joint. However, the diagnosis of gout may be challenging in the elderly because atypical presentations are more common in this group. Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid conditions such as chronic kidney disease, peptic ulcer disease and congestive heart failure may make the use of these agents dangerous or contraindicated. Thus, it is important to try to treat an acute flare of gout at the earliest sign, because the sooner treatment is initiated, the faster the inflammation will resolve. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used judiciously in the elderly. However, if used at the lowest dose that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the body will be eliminated, acute flares will no longer occur and tophi will resolve. Gout is often seen in association with hypertension, excessive alcohol consumption, obesity and hypertriglyceridaemia. These conditions and the medications used to treat them may contribute to the hyperuricaemia. Treating these conditions and using medications that do not promote hyperuricaemia will aid in the management of gout. Despite the challenges that often complicate the management of gout in the elderly, an understanding of the pathophysiology of the disease and both the indications and limitations of the medications used should allow successful treatment.
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PMID:Management of gout in older adults: barriers to optimal control. 1723 45

Uric acid and oxidative stress promote cardiovascular diseases, including atherosclerosis and hypertension. Xanthine oxidase, through which uric acid is generated, is a free-radical generating enzyme. The aim of the current study was to investigate whether allopurinol, an inhibitor of xanthine oxidase activity, affects vascular remodeling and vascular smooth muscle cell (VSMC) proliferation. In the carotid artery ligation model using spontaneously hypertensive rats (SHR), treatment with allopurinol induced a reduction in the neointima/media ratio by 27% (38.5+/-34.3% in the control group and 28.1 20.8% in the allopurinol-treated group, respectively, p<0.01) without alterations in vascular circumference at 3 weeks after ligation when compared to the control. Allopurinol lowered the serum uric acid concentration (147.0+/-3.6 micromol/l in the control group and 16.1+/-3.6 micromol/l in the allopurinol-treated group, respectively p<0.01) and xanthine oxidase activity, but not the blood pressure. In an in vitro study, high concentrations of uric acid (100 and 200 micromol/l) stimulated VSMC growth, but there was no stimulation of these cells by a low concentration of uric acid (50 micromol/I) or by any of three concentrations of xanthine (50, 100 and 200 micromol/l). In addition, allopurinol (5 micromol/I) had no effect on the cell growth. In conclusion, uric acid is a potent stimulator of VSMC proliferation, and allopurinol prevented vascular remodeling in SHR at least in part by inhibiting uric acid concentration.
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PMID:Allopurinol reduces neointimal hyperplasia in the carotid artery ligation model in spontaneously hypertensive rats. 1734 92

Uric acid is considered a major antioxidant in human blood that may protect against aging and oxidative stress. Despite its proposed protective properties, elevated levels of uric acid are commonly associated with increased risk for cardiovascular disease and mortality. Furthermore, recent experimental studies suggest that uric acid may have a causal role in hypertension and metabolic syndrome. All these conditions are thought to be mediated by oxidative stress. In this study we demonstrate that differentiation of cultured mouse adipocytes is associated with increased production of reactive oxygen species (ROS) and uptake of uric acid. Soluble uric acid stimulated an increase in NADPH oxidase activity and ROS production in mature adipocytes but not in preadipocytes. The stimulation of NADPH oxidase-dependent ROS by uric acid resulted in activation of MAP kinases p38 and ERK1/2, a decrease in nitric oxide bioavailability, and an increase in protein nitrosylation and lipid oxidation. Collectively, our results suggest that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. Since oxidative stress in the adipose tissue has recently been recognized as a major cause of insulin resistance and cardiovascular disease, hyperuricemia-induced alterations in oxidative homeostasis in the adipose tissue might play an important role in these derangements.
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PMID:Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. 1742 37

This study investigates the impact of uric acid (UA) on the risk factors associated with metabolic syndrome. In addition, this study explores the relationship between UA and insulin resistance and serum leptin levels in metabolic syndrome. A total of 470 subjects (252 women and 218 men) were recruited from the Department of Health Management at Chang Gung Medical Center (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment Panel III (ATP III) definition. The formula for the homeostasis model assessment of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45 subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52 males) (24.5%) were diagnosed as having metabolic syndrome. Patients with hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride (Tg) level. The subjects also had lower high-density lipoprotein and greater hypertension. Hormone assays showed an elevation of leptin, immunoreactive insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be better correlated with Tg, blood pressure (both systolic and diastolic), obesity, immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff value. Otherwise, there was no difference in leptin value. In conclusion, serum UA is significantly related to risk factors of metabolic syndrome except for blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in subjects with and without metabolic syndrome.
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PMID:Serum uric acid and leptin levels in metabolic syndrome: a quandary over the role of uric acid. 1751 6

Recent epidemiological studies provide a clear evidence that hyperuricemia is associated with hypertension, coronary heart disease, left ventricular hypertrophy and progression of renal disease. Aim of our study was to assess the effect of low dosage of recombinant urate oxidase on hyperuricemia in renal failure patients that already receiving allopurinol. Our study group consisted of 43 renal failure patients, 23 women and 20 men. The mean age was 74 years (range 36-90 years). The following variables were studied on admission: serum creatinine, blood urea nitrogen and serum uric acid. Intravenous rasburicase was administered at a dose of 0.02 mg/kg/day on 3 consecutive days in patients with serum uric acid between 8-10 mg/dl, on 5 consecutive days in patients with serum uric acid between 10-15 mg/dl and on 7 consecutive days in patients with serum uric acid > 15 mg/dl. Uric acid levels were assayed after 48 hours and 7 days after rasburicase treatment. Mean values of uric acid levels after 48 hours were 2.47 mg/dl (+/- 1.58) in men and 2.77 mg/dl (+/- 2.24) in woman, where'as mean values of uric acid levels after 7 days were 4.45 mg/dl (+/- 2.0) in men and 5.75 mg/dl (+/- 1.9) in woman. No significant relationship were found between uric acid and creatinine as before as well after therapy. There were no side effects in all patients included in the study. After 7 days, the rasburicase therapy showed more antihyperuricemic effect in men (59%) than in women (46%).
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PMID:Is rasburicase an effective alternative to allopurinol for management of hyperuricemia in renal failure patients? A double blind-randomized study. 1797 Feb 34

Hyperuricemia is a common finding in preeclamptic pregnancies evident from early pregnancy. Despite the fact that elevated uric acid often pre-dates the onset of clinical manifestations of preeclampsia, hyperuricemia is usually considered secondary to altered kidney function. Increased serum uric acid is associated with hypertension, renal disease and adverse cardiovascular events in the non-pregnant population and with adverse fetal outcomes in hypertensive pregnancies. We hypothesize that an elevated concentration of uric acid in preeclamptic women is not simply a marker of disease severity but rather contributes directly to the pathogenesis of the disorder. Using epidemiological and experimental evidence, gained largely outside of pregnancy, we will propose pathogenic roles for uric acid in preeclamptic pregnancies. Uric acid's ability to promote inflammation, oxidative stress and endothelial dysfunction will be highlighted with discussions of the potential impact on placental development and function and maternal vascular health.
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PMID:Uric acid as a pathogenic factor in preeclampsia. 1809 48

Appropriate parameters are needed for the monitoring of children with pulmonary arterial hypertension (PAH). Various biologic markers seem to be of use in adults with PAH. No data are available on their value in children with PAH. In this study, the relation between serum markers, functional parameters, and hemodynamic variables in pediatric PAH and their ability to predict survival is determined. Serum N-terminal pro brain natriuretic peptide (NT-proBNP), uric acid, norepinephrine, and epinephrine were measured and correlated with invasive hemodynamics, functional parameters, and outcome in 29 pediatric patients with PAH who visited a tertiary reference center for pediatric PAH between 1997 and 2005. NT-proBNP correlated with functional class (R = 0.36; p = 0.03) and 6-min walking distance (6MWD) (R = -0.53; p < 0.001). Uric acid correlated with mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index (R = 0.63, p = 0.01; R = 0.71, p = 0.03, and R = -0.65, p = 0.007, respectively). After initiation of treatment, NT-proBNP decreased. This decrease correlated with an increased 6MWD. Finally, norepinephrine and NT-proBNP levels were highly predictive for mortality. In this series of children with PAH, biologic markers were correlated with hemodynamics and functional capacity, as parameters of disease severity. The data indicate that these markers can be used to monitor treatment effects and predict mortality in pediatric PAH.
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PMID:Biological serum markers in the management of pediatric pulmonary arterial hypertension. 1828 71

Uric acid may mediate aspects of the relationship between hypertension and kidney disease via renal vasoconstriction and systemic hypertension. To investigate the relationship between uric acid and subsequent reduced kidney function, limited-access data of 13,338 participants with intact kidney function in two community-based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular Health Study, were pooled. Mean baseline serum uric acid was 5.9 +/- 1.5 mg/dl, mean baseline serum creatinine was 0.9 +/- 0.2 mg/dl, and mean baseline estimated GFR was 90.4 +/- 19.4 ml/min/1.73 m(2). During 8.5 +/- 0.9 yr of follow-up, 712 (5.6%) had incident kidney disease defined by GFR decrease (>or=15 ml/min/1.73 m(2) with final GFR <60 ml/min/1.73 m(2)), while 302 (2.3%) individuals had incident kidney disease defined by creatinine increase (>or=0.4 mg/dl with final serum creatinine >1.4 mg/dl in men and 1.2 mg/dl in women). In GFR- and creatinine-based logistic regression models, baseline uric acid level was associated with increased risk for incident kidney disease (odds ratio 1.07 [95% confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21] per 1-mg/dl increase in uric acid, respectively), after adjustment for age, gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin, hematocrit, baseline kidney function and cohort; therefore, elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population.
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PMID:Uric acid and incident kidney disease in the community. 1833 81

Hyperuricemia is associated with primary hypertension (HTN) in adults and children. Furthermore, uric acid levels during childhood are associated with blood pressure (BP) levels in adulthood. We measured 24-h ambulatory BP and serum uric acid (SUA) in 104 children referred for possible hypertension. Mean age was 13.7 +/- 2.6 y (range, 7-18 y) with 67 males and 37 females; 74 were African-American, 29 Caucasian and one Asian. SUA was associated with age (r = 0.38, p = 0.0001) and BMI Z-score (r = 0.23, p = 0.021). SUA was significantly associated with mean ambulatory systolic (S) and diastolic (D) BP. Mean ambulatory BP was normalized to gender- and height-specific reference standards using BP index. SUA was significantly associated with 24-h DBP index and nocturnal DBP index after adjusting for age, gender, race, BMI Z-score and urinary sodium excretion. SUA was also significantly associated with 24-h DBP load and nocturnal DBP load. Uric acid was significantly associated with increased likelihood for diastolic HTN (OR = 2.1, CI = 1.2, 3.7; p = 0.0063) after adjusting for other co-variables. Among children at risk for HTN, the likelihood for diastolic HTN (as defined by ambulatory blood pressure monitoring) increases significantly as SUA increases. SUA may be associated with increased severity of HTN during youth.
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PMID:Serum uric acid and ambulatory blood pressure in children with primary hypertension. 1859 75

Uric acid, despite being a major antioxidant in the human plasma, both correlates and predicts development of obesity, hypertension, and cardiovascular disease, conditions associated with oxidative stress. While one explanation for this paradox could be that a rise in uric acid represents an attempted protective response by the host, we review the evidence that uric acid may function either as an antioxidant (primarily in plasma) or pro-oxidant (primarily within the cell). We suggest that it is the pro-oxidative effects of uric acid that occur in cardiovascular disease and may have a contributory role in the pathogenesis of these conditions.
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PMID:Uric acid: the oxidant-antioxidant paradox. 1860 May 14


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